Latest Review Date: February 2025

Category: Laboratory           

DRAFT

POLICY:

Coverage may be subject to legislative mandates, including but not limited to the following, which applies prior to the policy:

• Minnesota Statue: 62Q.473 Biomarker Testing

Effective for dates of service on and after May 5, 2025:

I. Genetic Counseling

Genetic testing for hereditary breast and/or ovarian cancer may be considered medically necessary when ALL of the following criteria for genetic counseling are met along with criteria in sections II, IV, or V below:

• A recommendation for testing is confirmed by ONE of the following:
  • A physician who is certified by the American Board of Medical Genetics and Genomics or has active candidate status for certification who has no financial relationship with the testing laboratory*;
  • An American Board of Medical Genetics and Genomics or American Board of Genetic Counseling certified or certification eligible Genetic Counselor who has no financial relationship with the testing laboratory*;
  • A nurse credentialed as either a Genetic Clinical Nurse (GCN) or an Advanced Practice Nurse in Genetics (APNG) by either the Genetic Nursing Credentialing Commission (GNCC) or the American Nurses Credentialing Center (ANCC) who has no financial relationship with the testing laboratory*;
  • An oncologist or a surgical oncologist who has no financial relationship with the testing laboratory*; 
• The ordering healthcare professional (e.g., physician, genetic counselor, nurse, oncologist, surgeon) has no financial relationship with the testing laboratory. Note: Genetics professionals are not excluded if they are employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself.
• AND
• Content of counseling includes the following:
  • Evaluation of a 3-generation pedigree; and
  • Discussion of ALL of the following with the individual who is considering testing:
    • When clinically appropriate, options for surveillance and risk reduction (e.g., lifestyle, chemoprevention, risk-reducing surgery) for individuals with positive results, individuals with negative results, and key differences between the two; AND
    • Potential for uninformative or uncertain test results; AND
    • Potential that test results may provide health information regarding the risk of disease for other family members.

*Genetics professionals are not excluded if they are employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself.

II. Known Familial Mutation

Single-site (known familial variant) analysis of BRCA1, and/or BRCA2, and/or PALB2 may be considered medically necessary for an individual who meets ALL of the following:

• Genetic counseling criteria in section I have been met; AND
• Known familial mutation in BRCA1, and/or BRCA2, and/or PALB2 identified in 1st, 2nd, or 3rd degree relative(s); AND
• No previous germline BRCA1, and/or BRCA2, and/or PALB2 testing or results of previous testing were incomplete.

III. Personal History of Cancer

Genetic testing of BRCA1, and/or BRCA2, and/or PALB2 may be considered medically necessary for an individual who meets ALL of the following:

• Testing recommended by the treating surgeon, oncologist, or genetic counselor; AND
• Personal history of one or more of the following at any age:
  • Breast cancer
  • Ovarian cancer
  • Fallopian tube cancer
  • Primary peritoneal cancer
  • Pancreatic cancer
  • Prostate cancer that meets at least ONE of the following:
    1. Metastatic; OR
    2. Intraductal/cribriform histology ; OR-
    3. High-grade or very-high risk group defined as any of the following: 
       • Gleason score ≥ 8; OR
       • T stage of T3a, T3b, or T4; OR
       • Grade Group 4 or 5; OR
       • PSA > 20 ng/mL; OR
       • Gleason pattern 5 histology; or
    4. Ashkenazi Jewish ancestry; OR
    5. One or more close blood relative(s) with:
       • breast cancer age ≤ 50 years; OR
       • colorectal cancer age  ≤ 50 years; OR
       • endometrial cancer  ≤ 50 years; or
       • ovarian cancer at any age; OR
       • pancreatic cancer at any age; OR
       • metastatic, regional, very-high risk, high risk prostate cancer at any age; OR
    6. Two or more close blood relatives, on the same side of the family, with: breast or prostate cancer at any age; or
• AND
• No previous germline BRCA1, and/or BRCA2, and/or PALB2 testing; or results of previous testing were incomplete. 

IV. Predisposition Testing in Individuals with No Personal History of Cancers in Section III

Genetic testing of BRCA1, and/or BRCA2, and/or PALB2 may be considered medically necessary for an individual with no personal history of cancers listed in section III of this policy who meets ALL of the following:

• Genetic counseling criteria in section I have been met; AND
• A first-or second-degree blood relative meets any of the criteria in section III of this policy; AND
• Has a reasonable likelihood of a mutation based on pre-test genetic counseling; AND
• Individuals affected or unaffected with breast cancer and/or ovarian cancer who otherwise do not meet the criteria above but have a probability >5% of a BRCA1/2 pathogenic/likely pathogenic (P/LP) variant based on prior probability models (e.g., Tyrer-Cuzick, BRCAPro, CanRisk); AND
• Unaffected member is the most informative person to test. All affected family members are deceased, or all affected family members have been contacted and are unwilling to be tested; AND
• No previous germline BRCA1, and/or BRCA2, and/or PALB2 testing; or results of previous testing were incomplete. 

V. Multi-Gene Panel Sequencing

Genetic testing for hereditary breast and/or ovarian cancer using a multi-gene sequencing panel that includes BRCA1/BRCA2/PALB2 genes may be considered medically necessary when an individual meets ALL of the following:

• Genetic counseling meeting criteria in section I documents a family history/pedigree demonstrating a reasonable likelihood for one of the following cancer syndromes (associated genes in parentheses):
  • Bannayan-Riley-Ruvalcaba syndromes, Cowden syndrome (CS), PTEN hamartoma tumor syndrome (PTEN)
  • Hereditary diffuse gastric cancer syndrome (CDH1)
  • Li Fraumeni syndrome (TP53)
  • Lynch syndrome/hereditary non-polyposis colorectal cancer (MSH2, MLH1, MSH6, MUYH, PMS2, PMS1, EPCAM)
  • PALB2 genetic mutation associated with increased risk of breast cancer (PALB2)
  • Peutz-Jeghers syndrome (STK11) 
• AND
• Unaffected member is the most informative person to test. All affected family members are deceased, or all affected family members have been contacted and are unwilling to be tested; AND
• The majority of genes in the panel have a proven association with breast and/or ovarian cancer (e.g. ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, TP53); AND
• Results of testing will impact the medical management of the individual (e.g., increased screening or surveillance).

VI. Investigational

Genetic testing for hereditary breast and/or ovarian cancer as either a single-gene or multi-gene panel test is considered investigational for all other indications, including, but not limited to, the following due to a the lack of clinical evidence demonstrating an effect impact on improved health outcomes:

• Testing will not affect treatment or surveillance decisions
• Testing offered as a direct access (also known as direct to consumer)
• Testing in the general population as a screening tool
• All other testing for risk of hereditary breast and/or ovarian cancer that do not meet criteria as stated above.

Documentation Submission

Documentation from the ordering clinician supporting the medical necessity criteria in the policy must be included in the prior authorization. In addition, the following documentation must be submitted:

• The request states the specific test(s) name and included genes, AND
• Documentation from the clinical notes that criteria for genetic counseling (if required) have been met, AND
• Documentation of one of the following:
  • Known deleterious mutation in genes addressed in this policy in a close blood relative; OR
  • Diagnosis of individual with personal history of cancers addressed in this policy; OR
  • Results of pedigree indicating need for testing in individual with family history only; OR
  • Results of pedigree and genes for which multigene panel testing is indicated

1. The request states the specific test(s) name and included genes, AND
2. Documentation from the clinical notes that criteria for genetic counseling (if required) have been met, AND
3. Documentation of one of the following: 
   • Known deleterious mutation in genes addressed in this policy in a close blood relative; OR
   • Diagnosis of individual with personal history of cancers addressed in this policy; OR 
   • Results of family history indicating need for testing.

Effective for dates of service on and after May 6, 2024 through May 4, 2025:

I. Genetic Counseling

Genetic testing for hereditary breast and/or ovarian cancer may be considered medically necessary when ALL of the following criteria for genetic counseling are met along with criteria in sections II, IV, or V below:

• A recommendation for testing is confirmed by ONE of the following:
  • A physician who is certified by the American Board of Medical Genetics and Genomics or has active candidate status for certification who has no financial relationship with the testing laboratory*;
  • An American Board of Medical Genetics and Genomics or American Board of Genetic Counseling certified or certification eligible Genetic Counselor who has no financial relationship with the testing laboratory*;
  • A nurse credentialed as either a Genetic Clinical Nurse (GCN) or an Advanced Practice Nurse in Genetics (APNG) by either the Genetic Nursing Credentialing Commission (GNCC) or the American Nurses Credentialing Center (ANCC) who has no financial relationship with the testing laboratory*;
  • An oncologist or a surgical oncologist who has no financial relationship with the testing laboratory*; 
• AND
• Content of counseling includes BOTH of the following:
  • Evaluation of a 3-generation pedigree; and
  • Discussion of ALL of the following with the individual who is considering testing:
    • When clinically appropriate, options for surveillance and risk reduction (e.g., lifestyle, chemoprevention, risk-reducing surgery) for individuals with positive results, individuals with negative results, and key differences between the two; and
    • Potential for uninformative or uncertain test results; and
    • Potential that test results may provide health information regarding the risk of disease for other family members.

*Genetics professionals are not excluded if they are employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself.

II. Known Familial Mutation

Single-site (known familial variant) analysis of BRCA1 and/or BRCA2 may be considered medically necessary for an individual who meets ALL of the following:

• Genetic counseling criteria in section I have been met; AND
• Known familial mutation in BRCA1 and or BRCA2 identified in 1st, 2nd, or 3rd degree relative(s); AND
• No previous germline BRCA1 and/or BRCA2 testing or results of previous testing were incomplete.

III. Personal History of Cancer

Genetic testing of BRCA1 and/or BRCA2 may be considered medically necessary for an individual who meets ALL of the following:

• Testing recommended by the treating surgeon, oncologist, or genetic counselor; AND
• Personal history of one or more of the following at any age:
  • Breast cancer
  • Ovarian cancer
  • Fallopian tube cancer
  • Primary peritoneal cancer
  • Pancreatic cancer
  • Prostate cancer that meets at least one of the following:
    1. Metastatic; or
    2. Intraductal/cribriform histology ; or
    3. High-grade or very-high risk group defined as any of the following: 
       • Gleason score ≥ 8; or
       • T stage of T3a, T3b, or T4; or
       • PSA > 20 ng/mL; or
       • Gleason pattern 5 histology; or
    4. Ashkenazi Jewish ancestry; or
    5. One or more close blood relative(s) with:
       • breast cancer age ≤ 50 years; or
       • colorectal cancer age  ≤ 50 years; or
       • endometrial cancer  ≤ 50 years; or
       • ovarian cancer at any age; or
       • pancreatic cancer at any age; or,
       • metastatic, regional, very-high risk, high risk prostate cancer at any age; or
    6. Two or more close blood relatives, in the same side of the family,  with: breast or prostate cancer at any age;
• AND
• No previous germline BRCA1 and/or BRCA2 testing; or results of previous testing were incomplete. 

IV. Predisposition Testing in Individuals with No Personal History of Cancers in Section III

Genetic testing of BRCA1 and/or BRCA2 may be considered medically necessary for an individual with no personal history of cancers listed in section III of this policy who meets ALL of the following:

• Genetic counseling criteria in section I have been met; AND
• A first-or second-degree blood relative meets any of the criteria in section III of this policy; AND
• Has a reasonable likelihood of a mutation based on pre-test genetic counseling; AND
• Unaffected member is the most informative person to test. All affected family members are deceased, or all affected family members have been contacted and are unwilling to be tested; AND
• No previous germline BRCA1 and/or BRCA2 testing; or results of previous testing were incomplete. 

V. Multi-Gene Panel Sequencing

Genetic testing for hereditary breast and/or ovarian cancer using a multi-gene sequencing panel that includes BRCA1/BRCA2 genes may be considered medically necessary when an individual meets ALL of the following:

• Genetic counseling meeting criteria in section I documents a family history/pedigree demonstrating a reasonable likelihood for one of the following cancer syndromes (associated genes in parentheses):
  • Bannayan-Riley-Ruvalcaba syndromes, Cowden syndrome, PTEN hamartoma syndrome (PTEN)
  • Hereditary diffuse gastric cancer syndrome (CDH1)
  • Li Fraumeni syndrome (TP53)
  • Lynch syndrome/hereditary non-polyposis colorectal cancer (MSH2, MLH1, MSH6, MUYH, PMS2, PMS1, EPCAM)
  • PALB2 genetic mutation associated with increased risk of breast cancer (PALB2)
  • Peutz-Jeghers syndrome (STK11) 
• AND
• Unaffected member is the most informative person to test. All affected family members are deceased, or all affected family members have been contacted and are unwilling to be tested; AND
• The majority of genes in the panel have a proven association with breast and/or ovarian cancer (e.g. ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, TP53); AND
• Results of testing will impact the medical management of the individual (e.g., increased screening or surveillance).

VI. Investigational

Genetic testing for hereditary breast and/or ovarian cancer as either a single-gene or multi-gene panel test is considered investigational for all other indications, including, but not limited to, the following due to a lack of clinical evidence demonstrating an effect on health outcomes:

• Testing will not affect treatment or surveillance decisions
• Testing offered as a direct access (also known as direct to consumer)
• Testing in the general population as a screening tool
• All other testing for risk of hereditary breast and/or ovarian cancer that do not meet criteria as stated above.

Documentation Submission

Documentation from the ordering clinician supporting the medical necessity criteria in the policy must be included in the prior authorization. In addition, the following documentation must be submitted:

• The request states the specific test(s) name and included genes, AND
• Documentation from the clinical notes that criteria for genetic counseling (if required) have been met, AND
• Documentation of one of the following:
  • Known deleterious mutation in genes addressed in this policy in a close blood relative; OR
  • Diagnosis of individual with personal history of cancers addressed in this policy; OR
  • Results of pedigree indicating need for testing in individual with family history only; OR
  • Results of pedigree and genes for which multigene panel testing is indicated

DESCRIPTION OF PROCEDURE OR SERVICE:

Several genetic cancer syndromes with an autosomal dominant pattern of inheritance associated with an increased risk of breast or ovarian cancer have been identified. Genes included in this policy are those associated with hereditary breast and/or ovarian cancer syndromes that have been shown to have high penetrance, meaning that a large proportion of individuals with certain mutations in the gene will develop the disorder.

Genetic testing for cancer susceptibility may be approached by a focused method that involves testing for well-characterized mutations based on a clinical suspicion of which gene(s) may be the cause of the familial cancer. Panel testing involves testing for multiple mutations in multiple genes at one time.

Several companies offer genetic testing panels for assessing risk of hereditary cancers that use next generation sequencing methods. Next generation sequencing refers to one of several methods that use massively parallel platforms to allow the sequencing of large numbers of DNA segments. Panel testing is potentially associated with greater efficiencies in evaluating genetic diseases; however, it may provide information on genetic variants of unclear clinical significance or which would not lead to changes in patient management.

Genetic Counseling

Determining the appropriateness of genetic testing for a particular individual can be complex due to the many personal and family history factors that must be taken into consideration to determine which, if any, test is appropriate. Interpretation of test results and discussion of the possible health implications for the patient and family members are also important considerations. 

Definitions

Close Blood Relative: For the purposes of this policy, a relative is someone who is related by blood; a first-, second-, or third-degree relative from the same side of the family.

• First degree relative:  A family member who shares about 50 percent of their genes with a particular individual in a family. First degree relatives include parents, offspring, and siblings.
• Second degree relative:  A family member who shares about 25 percent of their genes with a particular individual in a family. Second degree relatives include grandparents, grandchildren, uncles, aunts, nephews, nieces, and half-siblings.
• Third degree relative:  A family member who shares about one-eighth of their genes, such as first cousins, great-grandparents, great-aunts, great-uncles.

Unaffected Member

The purpose of this genetic testing is to help inform a person’s likelihood of developing a specific condition, increased risk of developing a condition, or of passing on a genetic condition to their children. Testing should be considered in appropriate individuals where it is likely to impact the risk management and/or treatment of the tested individuals and/or their family members who also have increased risk. For the purpose of this policy, an unaffected member is one that has no personal history of breast and/or ovarian cancer and has not had testing to determine if genetic variants increase their risk of developing breast and/or ovarian cancer.

Affected Family Member

For the purpose of this policy, an affected family member is one that has a history of breast and/or ovarian cancer or has a history of another cancer that thereby increases the risk of the development of breast and/or ovarian cancer (i.e. fallopian tube cancer, primary peritoneal cancer, pancreatic cancer, or prostate cancer)

Gleason score is the preferred system for histopathological grading of prostate cancer. The score reflects the differentiation of cells in primary and secondary patterns. The combined scores from each pattern may range from 2-10. A Gleason score of 7 indicates a moderately aggressive tumor with intermediate differentiation (Grade Group 2 or 3). A score of 8 or greater indicates poorly differentiated or undifferentiated cells and a more aggressive tumor (Grade Group 4 or 5).

Lynch Syndrome-related cancers include colorectal, endometrial, gastric, ovarian, exocrine pancreatic, upper tract urothelial, glioblastoma, biliary tract, and small intestinal cancers.

Germline: Hereditary variant identified through a blood or saliva sample.

NOTES:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

• This policy only addresses genetic testing for breast and/or ovarian cancer.

KEY POINTS

The most recent literature reviewed completed through February 2025.

Summary of Evidence

Hereditary breast and ovarian cancer (HBOC) is an inherited form of cancer. About 1 in 400-500 people in the general population has a BRCA1 or BRCA2 mutation. The prevalence of mutations is higher in people of Norwegian, Dutch, Greenland, or Icelandic ethnicity. The prevalence of BRCA mutations varies among African Americans, Hispanics, Asian Americans, and non-Hispanic whites. About 1 in 40 people of Ashkenazi Jewish ancestry has a BRCA1 or BRCA2 mutation. Most of the risk in the Ashkenazi Jewish population is associated with three common founder mutations, two of which are in the BRCA1 gene and one in the BRCA2 gene. People with a BRCA mutation have an increased risk of various types of cancer. Up to 10% of all breast cancer and 15% of all ovarian cancer is associated with an inherited gene mutation, with BRCA1 and BRCA2 accounting for about 20-25% of all hereditary cases. 

In women with a family history of breast cancer, the prevalence of pathogenic PALB2 variants ranges between 0.9% and 3.9%, or substantially higher than in an unselected general population. Depending on population prevalence, PALB2 may be responsible for as much as 2.4% of hereditary breast cancers, and in populations with founder mutations cause 0.5% to 1% of all breast cancers. As additional genes and cancers are linked to the risk of developing breast and/or ovarian cancer, multigene panel testing has increased. 

Individuals and/or families with HBOC may have the following histories of cancer or other characteristics:

• breast cancer at a young age, typically under age 50
• multiple breast primaries in one individual and/or family members (on the same side of the family)
• triple negative breast cancer (ER-, PR-, HER2-)
• ovarian, fallopian tube, or primary peritoneal cancer
• metastatic (radiographic evidence of or biopsy-proven disease),
• intraductal/cribriform histology, high-risk, or very-high-risk group prostate cancer as defined by NCCN
• male breast cancer
• exocrine pancreatic cancer
• multiple cases of breast and/or ovarian cancer in a family or one individual with breast and ovarian cancer
• a confirmed diagnosis of prostate cancer and a family history of ovarian, breast, prostate, or pancreatic cancer
• previously identified germline BRCA1 or BRCA2 mutation in the family, or
• any of the above with Ashkenazi Jewish ancestry.

HBOC due to a mutation in BRCA1 or BRCA2 is an autosomal dominant disorder. In autosomal dominant inheritance, individuals have 2 copies of the gene and only one mutation is required to cause disease. When a parent has a mutation, each offspring has a 50% risk of inheriting the mutation. Males and females are equally likely to be affected. The diagnosis is established by the identification of a pathogenic mutation in a gene associated with HBOC. Screening and prevention options are available to specifically address the increased risk of these cancers in a person with a BRCA mutation. BRCA testing may include known familial mutation analysis, Ashkenazi Jewish founder mutation analysis, next generation sequencing, and/or deletion/duplication analysis.

PALB2 (partner and localizer of BRCA2) is a Fanconi anemia gene. PALB2 pathogenic/likely pathogenic (P/LP) variants are associated with increased risk for breast cancer, with studies of patients with breast cancer showing that 0.4% to 3% harbor a PALB2 P/LP variant. Fanconi anemia is a rare disorder, primarily affecting children, that causes bone marrow failure. Affected individuals also carry a risk of cancers including leukemia. Most pathogenic PALB2 variants are truncating frameshift or stop codons and are found throughout the gene. Pathogenic PALB2 variants are uncommon in unselected populations and prevalence varies by ethnicity and family history. Variants are more prevalent in ethnic populations where founder mutations have persisted (e.g., Finns, French Canadians, Poles), while infrequently found in others (eg, Ashkenazi Jews).

Practice Guidelines and Position Statement

The American College of Medical Genetics and Genomics (2019) issued a statement regarding BRCA1/2 testing in all individuals with breast cancer: “With the advances in sequencing technologies and increasing access to and expanding indications for genetic testing, it remains critical to ensure that implementation of testing is based on evidence. Currently, there is insufficient evidence to recommend genetic testing for BRCA1/2 alone or in combination with multi-gene panels for all breast cancer patients.”

The American Society of Breast Surgeons (2019) published a consensus guideline on genetic testing for hereditary breast cancer. They stated the following: "Breast surgeons, genetic counselors, and other medical professionals knowledgeable in genetic testing can provide patient education and counseling and make recommendations to their patients regarding genetic testing and arrange testing. When the patient’s history and/or test results are complex, referral to a certified genetic counselor or genetics professional may be useful. Genetic testing is increasingly provided through multi-gene panels. There are a wide variety of panels available, with different genes on different panels. There is a lack of consensus among experts regarding which genes should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in some genes. Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data supports the idea that genetic testing should be offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations (surgery and potentially radiation) and systemic therapy. Additionally, family members may subsequently be offered testing and tailored risk reduction strategies. Patients who had genetic testing previously may benefit from updated testing. Every patient being seen by a breast surgeon, who had genetic testing in the past and no pathogenic variant was identified, should be re-evaluated and updated testing considered. In particular, a patient who had negative germline BRCA1 and 2 testing, who is from a family with no pathogenic variants, should be considered for additional testing. Genetic testing performed prior to 2014 most likely would not have had PALB2 or other potentially relevant genes included and may not have included testing for large genomic rearrangements in BRCA1 or BRCA2. Genetic testing should be made available to patients without a history of breast cancer who meet NCCN guidelines. Unaffected patients should be informed that testing an affected relative first, whenever possible, is more informative than undergoing testing themselves. When it is not feasible to test the affected relative first, then the unaffected family member should be considered for testing if they are interested, with careful pre-test counseling to explain the limited value of “uninformative negative” results. It is also reasonable to order a multi-gene panel if the family history is incomplete (i.e., a case of adoption, patient is uncertain of exact type of cancer affecting family members, among others) or other cancers are found in the family history, as described above."

The National Comprehensive Cancer Network (NCCN, 2025) evidence and consensus-based guidelines addressed test indications for BRCA 1/2 and PALB2 testing. These guidelines included recommendations related to affected and unaffected individuals with a family history of cancer, those with a known mutation in the family, those with a personal history of breast cancer, exocrine pancreatic cancer, ovarian cancer, a confirmed diagnosis of prostate cancer, and men with breast cancer. They take into consideration age of diagnosis, tumor pathology, degree of relationship, and ethnicity.

U.S. Preventive Services Task Force Recommendations

The U.S. Preventive Services Task Force (2019) recommendations addressed women with a personal and/or family history of breast cancer and/or ovarian, tubal, or primary peritoneal cancer. The USPSTF guideline recommended: “When a woman's personal or family history of cancer is consistent with a BRCA1/2 mutation: “that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with breast cancer susceptibility 1 and 2 (BRCA1/2) gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. When a woman's personal or family history is not consistent with a BRCA1/2 mutation: “recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. Genetic risk assessment and BRCA1/2 mutation testing is a multistep process that begins with identifying patients with family or personal histories of breast, ovarian, tubal, or peritoneal cancer; family members with known harmful BRCA1/2 mutations; or ancestry associated with harmful BRCA1/2 mutations. Risk for clinically significant BRCA1/2 mutations can be further evaluated with genetic counseling by suitably trained health care clinicians, followed by genetic testing of selected high-risk individuals and posttest counseling about results. The type of mutation analysis required depends on family history. Individuals from families with known mutations or from ancestry groups in which certain mutations are more common (eg, Ashkenazi Jewish founder mutations) can be tested for these specific mutations."

APPROVED BY GOVERNING BODIES:

FDA approval is not currently required for these genetic tests. Clinical laboratories may develop and validate tests in-house ("home-brew") and market them as a laboratory service. The laboratory offering the service must be licensed by Clinical Laboratory Improvement Amendments (CLIA) for high-complexity testing.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefit. Group-specific policy will supercede this policy when applicable.

ITS: Home Policy provisions apply.

CURRENT CODING:

CPT codes:

0102U	Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with mRNA analytics to resolve variants of unknown significance when indicated (17 genes [sequencing and deletion/duplication])
0103U	Hereditary ovarian cancer (e.g., hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with mRNA analytics to resolve variants of unknown significance when indicated (24 genes [sequencing and deletion/duplication], EPCAM [deletion/duplication only])
0129U	Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis and deletion/duplication analysis panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, and TP53)
81162	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and full duplication/deletion analysis (i.e., detection of large gene rearrangements)
81163	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis
81164	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full duplication/deletion analysis (i.e., detection of large gene rearrangements)
81165	BRCA1 (BRCA1, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis
81166	BRCA1 (BRCA1, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full duplication/deletion analysis (i.e., detection of large gene rearrangements)
81167	BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full duplication/deletion analysis (i.e., detection of large gene rearrangements)
81212	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; 185delAG, 5385insC, 6174delT variants
81215	BRCA1 (BRCA1, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant
81216	BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis
81217	BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant
81307	PALB2 (partner and localizer of BRCA2) (e.g., breast and pancreatic cancer) gene analysis; full gene sequence
81308	PALB2 (partner and localizer of BRCA2) (e.g., breast and pancreatic cancer) gene analysis; known familial variant
81432	Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); genomic sequence analysis panel, must include sequencing of at least 10 genes, always including BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, and TP53
81479	Unlisted molecular pathology procedure

PREVIOUS CODING

81433

Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); duplication/deletion analysis panel, must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11 (deleted 12/31/24)

REFERENCES

1. Antoniou AC, Hardy R, Walker L, et al. Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics. J Med Genet. 2008;45(7):425-431.
2. Archer S, Babb de Villiers C, Scheibl F, et al. Evaluating clinician acceptability of the prototype CanRisk tool for predicting risk of breast and ovarian cancer: A multi-methods study. PLoS One. 2020;15(3):e0229999. Published 2020 Mar 6.
3. Bellcross CA. Hereditary Breast and Ovarian Cancer: An Updated Primer for OB/GYNs. Obstet Gynecol Clin North Am. 2022;49(1):117-147. 
4. Berliner JL, Cummings SA, Boldt Burnett B, Ricker CN. Risk assessment and genetic counseling for hereditary breast and ovarian cancer syndromes-Practice resource of the National Society of Genetic Counselors. J Genet Couns. 2021;30(2):342-360. 
5. Breast Cancer Association Consortium, Dorling L, Carvalho S, et al. Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med. 2021;384(5):428-439. 
6. Breast Cancer Association Consortium, Mavaddat N, Dorling L, et al. Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes. JAMA Oncol. 2022;8(3):e216744. 
7. Clinical Input. BCBSMN Medical Director. Received January 6, 2025.
8. Clinical Input. Certified Genetic Counselor, Tennessee. Received January 16, 2025.
9. D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer. 2002;95(2):281-286.
10. D'Amico AV, Whittington R, Malkowicz SB, et al. Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer. J Clin Oncol. 1999;17(1):168-172.
11. Epstein JI, Egevad L, Amin MB, et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol. 2016;40(2):244-252.
12. Hampel H et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1):70-87. Available at: www.acmg.net/docs/gim2014147a.pdf
13. Hu C, Hart SN, Gnanaolivu R, et al. A Population-Based Study of Genes Previously Implicated in Breast Cancer. N Engl J Med. 2021;384(5):440-451.
14. Kleibl Z, Kristensen VN. Women at high risk of breast cancer: Molecular characteristics, clinical presentation and management. Breast. 2016;28:136-144. 
15. Manahan ER, Kuerer HM, Sebastian M, et al. Consensus Guidelines on Genetic` Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons. Ann Surg Oncol. 2019;26(10):3025-3031. 
16. Minnesota Statutes 2025, section 62Q.473 Biomarker Testing; MINN. STAT 62Q.473. 2025. 
17. Murphy, C.D., Lee, J.M., Drohan, B., et al. The American Cancer Society guidelines for breast screening with magnetic resonance imaging. Cancer, (2008). 113: 3116-3120.
18. National Cancer Institute. BRCA gene mutations: cancer risk and genetic testing. Updated November 19, 2020. Available at: www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#r1
19. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. V.3.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf. 
20. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk  Assessment: Breast, Ovarian, Pancreatic, and Prostate version 2.2025. Updated November 7, 2024. Available at: www.nccn.org/professionals/physician_gls/pdf/genetics_bopp.pdf
21. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V4.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
22. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer version 1.2025. Updated December 4, 2024. Available at: www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
23. Norquist BM, Harrell MI, Brady MF, et al. Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol. 2016;2(4):482-490.
24. Pal T, Agnese D, Daly M, et al. Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(4):681-685. 
25. Parmigiani G, Chen S, Iversen ES Jr, et al. Validity of models for predicting BRCA1 and BRCA2 mutations. Ann Intern Med. 2007;147(7):441-450
26. Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. In: Adam MP, Feldman J, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; September 4, 1998.
27. Rubinstein WS. Hereditary breast cancer in Jews. Fam Cancer. 2004;3(3-4):249-257.  
28. Song H, Dicks EM, Tyrer J, et al. Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer. J Med Genet. 2021;58(5):305-313.
29. Suszynska M, Klonowska K, Jasinska AJ, Kozlowski P. Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes. Gynecol Oncol. 2019;153(2):452-462.
30. Tischkowitz M, Xia B. PALB2/FANCN: recombining cancer and Fanconi anemia. Cancer Res. 2010;70(19):7353-7359. 
31. Terry MB, Liao Y, Whittemore AS, et al. 10-year performance of four models of breast cancer risk: a validation study. Lancet Oncol. 2019;20(4):504-517. 
32. Tyrer-Cuzick Risk Assessment Calculator. Available at:ibis-risk-calculator.magview.com/. Last accessed: 2/3/2025.
33. U.S. Preventive Services Task Force (USPSTF). Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: recommendation statement. Available at: www.uspreventiveservicestaskforce.org
34. van der Groep P, van der Wall E, van Diest PJ. Pathology of hereditary breast cancer. Cell Oncol (Dordr). 2011;34(2):71-88. 
35. Walsh T, King MC. Ten genes for inherited breast cancer. Cancer Cell. 2007;11(2):103-105.  
36. Yadav S, Boddicker NJ, Na J, et al. Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 2023;41(9):1703-1713. 
37. Yang X, Leslie G, Doroszuk A, et al. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J Clin Oncol. 2020;38(7):674-685.

POLICY HISTORY:

Reviewed and posted July 1, 2021.

Reviewed and posted February 16, 2022.

Available for comment February 16, 2022 through March 4, 2022.

January 2023: Annual review complete. No change to policy intent. 

February 2024: Updates to Description, Key Points, and References. Policy statement updated to include revision of criteria in Section III: Personal History of Cancer – added on the same side of the family under close blood relatives and removed 3 or more close relatives with Lynch syndrome related cancers. Policy posted as draft March 18, 2024 through May 5, 2024.

October 2024: Minnesota statute 62Q.473 Biomarker testing verbiage added to policy.

December 2024: Annual Coding Update; CPT code 81433 deleted, effective 12/31/24. Moved CPT code from Current coding section to Previous coding section. 

February 2025: Updates to Minnesota State Statue

March 2025: Annual review complete. Updates to Description, Key Points, and References. Policy statement updated to include PALB2 testing. Policy posted as draft March 20, 2025 through May 4, 2025.

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This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.